tbuckley/cabot-search huggingface dataset:
Severity of COVID-19–Related Illness in Massachusetts, July 2021 to December 2022
Authors: Alaleh Azhir, Zachary H. Strasser, Shawn N. Murphy, Hossein Estiri
Journal: JAMA Network Open (2023)

This cohort study uses hospitalization and 30-day mortality risks to create a temporal profile of the severity of COVID-19 in Massachusetts from July 2021 to December 2022.
Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics
Authors: Lina Lu, Jennifer Rui Wang, Ying C. Henderson, Shanshan Bai, Jie Yang, Min Hu, Cheng-Kai Shiau, Timothy Pan, Yuanqing Yan, Tuan M. Tran, Jianzhuo Li, Rachel Kieser, Xiao Zhao, Jiping Wang, Roza Nurieva, Michelle D. Williams, Maria E. Cabanillas, Ramona Dadu, Naifa Lamki Busaidy, Mark Zafereo, Nicholas Navin, Stephen Y. Lai, Ruli Gao
Journal: Journal of Clinical Investigation (2023)

The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intra-tumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single cell transcriptomes and genetic alteration data from patients with different subtypes of thyroid cancer. The resulting spectrum of ATC transformation included stress-responsive DTC cells, inflammatory ATC cells (iATCs), mitotic-defective ATC cells and extended all the way to mesenchymal ATC cells (mATCs). Further, our analysis identified two important milestones: 1) a diploid stage, where iATC cells were diploids with inflammatory phenotypes, and 2) an aneuploid stage, where mATCs gained aneuploid genomes and mesenchymal phenotypes producing excessive collagens and collagen-interacting receptors. In parallel, cancer-associated-fibroblasts showed strong interactions among mesenchymal cell-types, macrophages shifted from M1 to M2 states, and T cells reprogrammed from cytotoxic to exhausted states, highlighting new therapeutic opportunities for ATC.
Prostate-Specific Antigen Screening Should Not Be Covered by Publicly Funded Health Insurance—Reply
Authors: Shuang Hao, Tobias Nordström, Mark S. Clements
Journal: JAMA Oncology (2023)

In Reply We read with interest the letter by Takahashi in response to our economic evaluation study.1 We agree with the author—and with most commentators—that there is currently insufficient evidence for introducing population-based, organized prostate cancer screening.
Chronic Pain Among Adults — United States, 2019–2021
Authors: S. Michaela Rikard, Andrea E. Strahan, Kristine M. Schmit, Gery P. Guy
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Chronic pain (i.e., pain lasting ≥3 months) is a debilitating condition that affects daily work and life activities for many adults in the United States and has been linked with depression (1), Alzheimer disease and related dementias (2), higher suicide risk (3), and substance use and misuse (4). During 2016, an estimated 50 million adults in the United States experienced chronic pain, resulting in substantial health care costs and lost productivity (5,6). Addressing chronic pain and improving the lives of persons living with pain is a public health imperative. Population research objectives in the National Pain Strategy, which was released in 2016 by the Interagency Pain Research Coordinating Committee, call for more precise estimates of the prevalence of chronic pain and high-impact chronic pain (i.e., chronic pain that results in substantial restriction to daily activities) in the general population and within various population groups to guide efforts to reduce the impact of chronic pain (3). Further, a 2022 review of U.S. chronic pain surveillance systems identified the National Health Interview Survey (NHIS) as the best source for pain surveillance data (7). CDC analyzed data from the 2019-2021 NHIS to provide updated estimates of the prevalence of chronic pain and high-impact chronic pain among adults in the United States and within population groups defined by demographic, geographic, socioeconomic, and health status characteristics. During 2021, an estimated 20.9% of U.S. adults (51.6 million persons) experienced chronic pain, and 6.9% (17.1 million persons) experienced high-impact chronic pain. New findings from this analysis include that non-Hispanic American Indian or Alaska Native (AI/AN) adults, adults identifying as bisexual, and adults who are divorced or separated are among the populations experiencing a higher prevalence of chronic pain and high-impact chronic pain. Clinicians, practices, health systems, and payers should vigilantly attend to health inequities and ensure access to appropriate, affordable, diversified, coordinated, and effective pain management care for all persons (8).
Time to negative throat culture following initiation of antibiotics for pharyngeal group A Streptococcus: a systematic review and meta-analysis up to October 2021 to inform public health control measures
Authors: Emma McGuire, Ang Li, Simon M Collin, Valerie Decraene, Michael Cook, Simon Padfield, Shiranee Sriskandan, Chris Van Beneden, Theresa Lamagni, Colin S Brown
Journal: Eurosurveillance (2023)

Background Public health guidance recommending isolation of individuals with group A streptococcal (GAS) infection or carriage for 12–24 h from antibiotic initiation to prevent onward transmission requires a strong evidence base. Aim To estimate the pooled proportion of individuals who remain GAS culture-positive at set intervals after initiation of antibiotics through a systematic literature review (PROSPERO CRD42021290364) and meta-analysis. Methods We searched Ovid MEDLINE (1946–), EMBASE (1974–) and Cochrane library. We included interventional or observational studies with ≥ 10 participants reporting rates of GAS throat culture positivity during antibiotic treatment for culture-confirmed GAS pharyngitis, scarlet fever and asymptomatic pharyngeal GAS carriage. We did not apply age, language or geographical restrictions. Results Of 5,058 unique records, 43 were included (37 randomised controlled studies, three non-randomised controlled trials and three before-and-after studies). The proportion of individuals remaining culture-positive on day 1, day 2 and days 3–9 were 6.9% (95% CI: 2.7–16.8%), 5.4% (95% CI: 2.1–13.3%) and 2.6% (95% CI: 1.6–4.2%). For penicillins and cephalosporins, day 1 positivity was 6.5% (95% CI: 2.5–16.1%) and 1.6% (95% CI: 0.04–42.9%), respectively. Overall, for 9.1% (95% CI: 7.3–11.3), throat swabs collected after completion of therapy were GAS culture-positive. Only six studies had low risk of bias. Conclusions Our review provides evidence that antibiotics for pharyngeal GAS achieve a high rate of culture conversion within 24 h but highlights the need for further research given methodological limitations of published studies and imprecision of pooled estimates. Further evidence is needed for non-beta-lactam antibiotics and asymptomatic individuals.
Circulating succinate-modifying metabolites accurately classify and reflect the status of fumarate hydratase–deficient renal cell carcinoma
Authors: Liang Zheng, Zi-Ran Zhu, Tal Sneh, Wei-Tuo Zhang, Zao-Yu Wang, Guang-Yu Wu, Wei He, Hong-Gang Qi, Hang Wang, Xiao-Yu Wu, Jonatan Fernández-García, Ifat Abramovich, Yun-Ze Xu, Jin Zhang, Eyal Gottlieb
Journal: Journal of Clinical Investigation (2023)

Germline or somatic loss-of-function mutations of fumarate hydratase (FH) predispose patients to an aggressive form of renal cell carcinoma (RCC). Since other than tumor resection, there is no effective therapy for metastatic FH-deficient RCC, an accurate method for early diagnosis is needed. Although MRI or CT scans are offered, they cannot differentiate FH-deficient tumors from other RCCs. Therefore, finding noninvasive plasma biomarkers suitable for rapid diagnosis, screening and surveillance would improve clinical outcomes. Taking advantage of the robust metabolic rewiring that occurs in FH-deficient cells, we performed plasma metabolomics analysis and identified two tumor-derived metabolites, succinyl-adenosine and succinic-cysteine, as outstanding plasma biomarkers for early diagnosis (receiver operating characteristic area under curve (ROCAUC) = 0.98). These two molecules reliably reflected the FH mutation status and tumor mass. We further identified the enzymatic cooperativity by which these biomarkers are produced within the tumor microenvironment. Longitudinal monitoring of patients demonstrated that these circulating biomarkers can be used for reporting on treatment efficacy and identifying recurrent or metastatic tumors.
<i>QuickStats:</i> Percentage* of Adults† Who Were in Families Having Problems Paying Medical Bills During the Previous 12 Months,§ by Race and Selected Hispanic¶ Origin Subgroups — National Health Interview Survey, United States, 2020−2021**
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Abbreviation: NH = non-Hispanic.* With 95% CIs indicated by error bars.† Estimates are based on household interviews of a sample of the civilian, noninstitutionalized U.S. population and are derived from the 2020 and 2021 National Health Interview Survey.§ "Problems paying medical bills" is based on a positive response to a question asking, "In the past 12 months, did you/ anyone in the family have problems paying or were unable to pay any medical bills?Include bills for doctors, dentists, hospitals, therapists, medication, equipment, nursing home, or home care." ¶ Hispanic or Latino includes all Hispanic adults, including other Hispanic origin subgroups not shown separately.** Total includes all adults, including other race groups not shown separately.During 2020-2021, the percentage of U.S. adults who were in families having problems paying medical bills during the previous 12 months was 11.3%.Non-Hispanic Black or African American adults (16.8%) were most likely to be in families having problems paying medical bills followed by Hispanic or Latino (13.5%), non-Hispanic White (10.0%), and non-Hispanic Asian (5.7%) adults.Among the Hispanic or Latino origin subgroups shown, the percentage of adults in families having problems paying medical bills ranged from 9.7% among Cuban to 18.8% among Puerto Rican adults.
Stein EM. IDH2 inhibition in AML. <i>Blood.</i> 2023;141(2):124-125.
Authors: Yao Wang, Zhiqiang Wu, Weidong Han, Dongyao Wang, Zimin Sun, Xiaoyu Zhu, Xiaohu Zheng, Yonggang Zhou, Yichen Lu, Peidong Yan, Huiru Wang, Huilan Liu, Jing Jin, Huaiping Zhu, Rui Sun, Yi Wang, Binqing Fu, Zhigang Tian, Haiming Wei
Journal: Blood (2023)
Evaluation of Body Mass Index, Overweight and Obesity Status, and Cholesterol Levels in Younger Children
Authors: Ursa Sustar, Olga Kordonouri, Stefan Arens, Jernej Kovac, Katarina Sedej, Tadej Battelino, Urh Groselj
Journal: JAMA Network Open (2023)

This cohort study examines cholesterol levels in children with overweight or obesity.
RuCu Nanosheets with Ultrahigh Nanozyme Activity for Chemodynamic Therapy
Authors: Jian Yang, Le Fang, Ruibin Jiang, Lubin Qi, Yating Xiao, Wenxi Wang, Ismail Ismail, Xiaohong Fang
Journal: Advanced Healthcare Materials (2023)

Nanoenzymes have been widely explored for chemodynamic therapy (CDT) in cancer treatment. However, poor catalytic efficiency of nanoenzymes, especially in the tumor microenvironment with insufficient H2 O2 and mild acidity, limits the effect of CDT. Herein, a new ultrathin RuCu nanosheet (NS) based nanoenzyme which has a large specific surface area and abundant channels and defects is developed. The RuCu NSs show superb catalytic efficiency for the oxidation of peroxidase substrate H2 O2 at a wide range of pH and their catalytic efficiency (kcat /Km = 177.2 m-1 s-1 ) is about 14.9 times higher than that of the single-atom catalyst FeN3 P. Besides being an efficient nanozyme as peroxidase, the RuCu NSs possess other two enzyme activities, not only disproportionating superoxide anion to produce H2 O2 but also consuming glutathione to keep a high concentration of H2 O2 in the tumor microenvironment for Fenton reaction. With these advantages, the RuCu NSs exhibit good performance to kill cancer cells and inhibit tumor growth in mice, demonstrating a promising potential as new CDT reagent.
Associations of minor histocompatibility antigens with outcomes following allogeneic hematopoietic cell transplantation
Authors: Othmane Jadi, Hancong Tang, Kelly Olsen, Steven Vensko, Qianqian Zhu, Yiwen Wang, Christopher A. Haiman, Loreall Pooler, Xin Sheng, Guy Brock, Amy Webb, Marcelo C. Pasquini, Philip L. McCarthy, Stephen R. Spellman, Theresa Hahn, Benjamin Vincent, Paul Armistead, Lara E. Sucheston‐Campbell
Journal: American Journal of Hematology (2023)

Abstract The role of minor histocompatibility antigens (mHAs) in mediating graft versus leukemia and graft versus host disease (GvHD) following allogeneic hematopoietic cell transplantation (alloHCT) is recognized but not well‐characterized. By implementing improved methods for mHA prediction in two large patient cohorts, this study aimed to comprehensively explore the role of mHAs in alloHCT by analyzing whether (1) the number of predicted mHAs, or (2) individual mHAs are associated with clinical outcomes. The study population consisted of 2249 donor–recipient pairs treated for acute myeloid leukemia and myelodysplastic syndrome with alloHCT. A Cox proportional hazard model showed that patients with a class I mHA count greater than the population median had an increased hazard of GvHD mortality (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.01, 1.77, p = .046). Competing risk analyses identified the class I mHAs DLRCKYISL ( GSTP ), WEHGPTSLL ( CRISPLD2 ), and STSPTTNVL ( SERPINF2 ) were associated with increased GVHD mortality (HR = 2.84, 95% CI = 1.52, 5.31, p = .01), decreased leukemia‐free survival (LFS) (HR = 1.94, 95% CI = 1.27, 2.95, p = .044), and increased disease‐related mortality (DRM) (HR = 2.32, 95% CI = 1.5, 3.6, p = .008), respectively. One class II mHA YQEIAAIPSAGRERQ ( TACC2 ) was associated with increased risk of treatment‐related mortality (TRM) (HR = 3.05, 95% CI = 1.75, 5.31, p = .02). WEHGPTSLL and STSPTTNVL were both present within HLA haplotype B*40:01‐C*03:04 and showed a positive dose–response relationship with increased all‐cause mortality and DRM and decreased LFS, indicating these two mHAs contribute to the risk of mortality in an additive manner. Our study reports the first large‐scale investigation of the associations of predicted mHA peptides with clinical outcomes following alloHCT.
Constructing Spatiotemporally Controllable Biocatalytic Cascade in RBC Nanovesicles for Precise Tumor Therapy Based on Reversibly Induced Glucose Oxidase‐Magnetoferritin Dimers
Authors: Xinjie Chen, Miaoliang Ruan, Jinpei Wu, Tianci Zhu, Yaoqi Wen, Xiaodi Li, Caiqi Yang, Xiaoqing Zong, Pengfei Yuan, Yuchao Li, Xiaodie Yan, Wei Xue, Jian Dai
Journal: Advanced Healthcare Materials (2023)

Chemodynamic therapy is a promising tumor treatment strategy. However, it remains a great challenge to overcome the unavoidable off-target damage to normal tissues. In this work, it is discovered that magnetoferritin (M-HFn, biomimic peroxidase) can form nanocomplexes with glucose oxidase (GOD) in the presence of glucose, thus inhibiting the enzyme activity of GOD. Interestingly, GOD&M-HFn (G-M) nanocomplexes can dissociate under near-infrared (NIR) laser, reactivating the enzyme cascade. Based on this new finding, a spatiotemporally controllable biocatalytic cascade in red blood cell (RBC) nanovesicles (G-M@RBC-A) is fabricated for precise tumor therapy, which in situ inhibits enzyme cascade between GOD and M-HFn during blood circulation and reactivates the cascade activity in tumor site by NIR laser irradiation. In RBC nanovesicles, GOD is grabbed by M-HFn to form G-M nanocomplexes in the presence of glucose, thus inhibiting the Fenton reaction and reducing side effects. However, after NIR laser irradiation, G-M nanocomplexes are spatiotemporally dissociated and the cascade activity is reactivated in the tumor site, initiating reactive oxygen species damage to cancer cells in vivo. Therefore, this work provides new insight into the fabrication of spatiotemporally controllable biocatalytic cascade for precise cancer therapy in the future.
Educational Outcomes in Children and Adolescents With Type 1 Diabetes and Psychiatric Disorders
Authors: Shengxin Liu, Jonas F. Ludvigsson, Paul Lichtenstein, Soffia Gudbjörnsdottir, Mark J. Taylor, Henrik Larsson, Ralf Kuja-Halkola, Agnieszka Butwicka
Journal: JAMA Network Open (2023)

Importance Research shows that children and adolescents with type 1 diabetes (T1D), compared with their peers without diabetes, have a greater risk of psychiatric disorders. However, no study has comprehensively examined whether having psychiatric disorders is associated with educational outcomes in children and adolescents with T1D. Objective To investigate educational outcomes in children and adolescents with T1D with and without psychiatric disorders. Design, Setting, and Participants This cohort study used data from multiple Swedish registers. The main study cohort included individuals born in Sweden between January 1, 1973, and December 31, 1997, who were followed up from birth through December 31, 2013. Data analyses were conducted from March 1 to June 30, 2022. Exposures Type 1 diabetes and psychiatric disorders (including neurodevelopmental disorders, depression, anxiety disorders, eating disorders, bipolar disorder, psychotic disorder, and substance misuse) diagnosed before 16 years of age. Main Outcomes and Measures Achieving educational milestones (completing compulsory school [primary and lower secondary education], being eligible to and finishing upper secondary school, and starting and finishing university) and compulsory school performances. Results Of 2 454 862 individuals (51.3% male), 13 294 (0.5%; 53.9% male) were diagnosed with T1D (median [IQR] age at diagnosis, 9.5 [6.0-12.5] years), among whom 1012 (7.6%) also had at least 1 psychiatric disorder. Compared with healthy individuals (without T1D and psychiatric disorders), individuals with T1D alone had slightly lower odds of achieving the examined educational milestones. However, those with both T1D and any psychiatric disorder had much lower odds of achieving milestones, including completing compulsory school (odds ratio [OR], 0.17; 95% CI, 0.13-0.21), being eligible for (OR, 0.25; 95% CI, 0.21-0.30) and finishing (OR, 0.19; 95% CI, 0.14-0.26) upper secondary school, and starting (OR, 0.36; 95% CI, 0.29-0.46) and finishing (OR, 0.30; 95% CI, 0.20-0.47) university. They also showed lower grade point averages for compulsory school subjects. These findings remained similar in sibling comparison analyses, suggesting independence from familial confounding. Conclusions and Relevance In this cohort study of Swedish-born children and adolescents, those with T1D alone had minor difficulties with their educational outcomes, whereas those with both T1D and psychiatric disorders had universal long-term educational underachievement. These findings highlight the importance of identifying psychiatric disorders in pediatric patients with T1D and the need for targeted educational intervention and support to minimize the education gap between the affected children and their peers.
CHARGE syndrome-associated CHD7 acts at ISL1-regulated enhancers to modulate second heart field gene expression
Authors: Athanasia Stathopoulou, Ping Wang, Charlotte Thellier, Robert G Kelly, Deyou Zheng, Peter J Scambler
Journal: Cardiovascular Research (2023)

Abstract Aims Haploinsufficiency of the chromo-domain protein CHD7 underlies most cases of CHARGE syndrome, a multisystem birth defect including congenital heart malformation. Context specific roles for CHD7 in various stem, progenitor, and differentiated cell lineages have been reported. Previously, we showed severe defects when Chd7 is absent from cardiopharyngeal mesoderm (CPM). Here, we investigate altered gene expression in the CPM and identify specific CHD7-bound target genes with known roles in the morphogenesis of affected structures. Methods and results We generated conditional KO of Chd7 in CPM and analysed cardiac progenitor cells using transcriptomic and epigenomic analyses, in vivo expression analysis, and bioinformatic comparisons with existing datasets. We show CHD7 is required for correct expression of several genes established as major players in cardiac development, especially within the second heart field (SHF). We identified CHD7 binding sites in cardiac progenitor cells and found strong association with histone marks suggestive of dynamically regulated enhancers during the mesodermal to cardiac progenitor transition of mESC differentiation. Moreover, CHD7 shares a subset of its target sites with ISL1, a pioneer transcription factor in the cardiogenic gene regulatory network, including one enhancer modulating Fgf10 expression in SHF progenitor cells vs. differentiating cardiomyocytes. Conclusion We show that CHD7 interacts with ISL1, binds ISL1-regulated cardiac enhancers, and modulates gene expression across the mesodermal heart fields during cardiac morphogenesis.
Hepatorenal syndrome: Current concepts and future perspectives
Authors: Chan-Young Jung, Jai Won Chang
Journal: Clinical and Molecular Hepatology (2023)

Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis, often leading to death before liver transplantation (LT). Recent updates in the pathophysiology, definition, and classification of HRS have led to a complete revision of the nomenclature and diagnostic criteria for HRS type 1, which was renamed HRS-acute kidney injury (AKI). HRS is characterized by severe impairment of kidney function due to increased splanchnic blood flow, activation of several vasoconstriction factors, severe vasoconstriction of the renal arteries in the absence of kidney histologic abnormalities, nitric oxide dysfunction, and systemic inflammation. Diagnosis of HRS remains a challenge because of the lack of specific diagnostic biomarkers that accurately distinguishes structural from functional AKI, and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The optimal treatment of HRS is LT. While awaiting LT, treatment options include vasoconstrictor drugs to counteract splanchnic arterial vasodilation and plasma volume expansion by intravenous albumin infusion. In patients with HRS unresponsive to pharmacological treatment and with conventional indications for kidney replacement therapy (KRT), such as volume overload, uremia, or electrolyte imbalances, KRT may be applied as a bridging therapy to transplantation. Other interventions, such as transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Although recently developed novel therapies have potential to improve outcomes of patients with HRS, further studies are warranted to validate the efficacy of these novel agents.